GB2586201A

GB2586201A - A stable powder formulation of racecadotril

Info

Publication number: GB2586201A
Application number: GB1906754.5A
Authority: GB
Inventors: Patel Hetalbahen
Original assignee: Orbit Pharmaceuticals
Current assignee: Orbit Pharmaceuticals
Priority date: 2019-05-14
Filing date: 2019-05-14
Publication date: 2021-02-17
Anticipated expiration: 2039-05-14
Also published as: GB2586201B; GB201906754D0

Abstract

A stable powder formulation of racecadotril comprising 0.1 to 2 % w/w of racecadotril, 15 to 25 % w/w of intragranular sweetener, binder dispersion comprising 1 to 5 wt.% of polymer and an auxiliary agent, 60 to 80 % w/w of extra granular sweetener, a flavouring agent and a glidant. Such a formulation may mask the taste of the racecadotril. Preferably, the acetorphan is in the free base form. Preferably, the auxiliary agent is selected from sorbitol, mannitol, sucralose, trehalose and lactose. Most preferably, the intra-granular and extra-granular sweetener is sucrose. The granules may be formed by wet granulation. In one embodiment, the formulation comprises (by wt.) 1 % racecadotril, 25 % intragranular sucrose, 2.5 % polymeric binder (ACRYCOAT (RTM) E 30 D, acrylate/methacrylate based polymer) with 0.14 % sucralose as auxiliary agent, 71 % extra granular sucrose, 0.2 % dry lemon flavour, and 0.2 % anhydrous colloidal silica as glidant. Also claimed is a method for preparing the powder formulation.

Description

Intellectual Property Office Application No. GII1906754.5 RTM Date:23 October 2020 The following terms are registered trade marks and should be read as such wherever they occur in this document: Eudragit Aerosil Hidrasec Intellectual Property Office is an operating name of the Patent Office www.gov.uk/ipo Title: A stable powder formulation of Racecadotril Field of the Invention The present invention relates to a stable powder formulation of Racecadotril. Particularly the present invention is all about a stable powder formulation of Racecadotril, intragranular sweetener, binder dispersion, extra granular sweetener, a flavouring agent and glidant. The present invention also relates to process for preparing a stable powder formulation of Racecadotril.

Background of the Invention

Diarrhea is an increase in the volume of stool or frequency of defecation. It is one of the most common clinical signs of gastrointestinal disease, but also can reflect primary disorders outside of the digestive system. Certainly, disorders affecting either the small or large bowel can lead to diarrhea.

For many people, diarrhea represents an occasional inconvenience or annoyance, yet at least 2 million people in the world, mostly children, die from the consequences of diarrhea each year.

There are numerous causes of diarrhea, but in almost all cases, this disorder is a manifestation of one of the four basic mechanisms described below. It is also common for more than one of the four mechanisms to be involved in the pathogenesis of a given case.

Diarrhea results when there is alteration of this normal physiologic process of digestion and absorption. There are multiple causes for diarrhea and there may be multiple pathophysiologic mechanisms for a single disease entity. Nonetheless, the following pathophysiologic classification provides a useful framework for approaching diarrhea: * Diarrhea secondary to altered mucosal transport or secretory dysfunction * Osmotic diarrhea Diarrhea secondary to malabsorption 25. Exudative diarrhea * Diarrhea secondary to altered bowel motility Racecadotril (acetorphan) is an oral enkephalinase inhibitor for use in the treatment of acute diarrhoea. By preventing the degradation of endogenous enkephalins, Racecadotril reduces hypersecreti on of water and electrolytes into the intestinal lumen. Treatment with Racecadotril reduces the incidence and duration of acute diarrhoea and reduces diarrhoea-associated symptoms compared with placebo in adults. Racecadotril treatment also results in significant reductions in stool output compared with placebo in infants and young children aged 2 months to 4 years with acute diarrhoea. Both rotavirus-negative and rotavirus-positive infections appear to respond to treatment in the paediatric populations investigated for this infection.

Racecadotril was first disclosed in US4513009 and it is used for diarrhoea treatment. 10 Racecadotril is also known as acetorphane Chemically Racecadotril is known as Benzyl 243-(acetylthio)-2-benzylpropanamido] acetate and chemical structure is as follow, Racecadotril is a class II drug (as per Biopharmaceutical Classification System) with poor aqueous solubility and dissolution rate limited absorption. Racecadotril undergoes hydrolysis when it comes into contact with water. Thiorphan (shown below) is the active metabolite of Racecadotril, which exerts the bulk of its inhibitory actions on enkephalinase.

The pharmaceutical products comprising Racecadotril are present in the market with the trade names Hidrasec, Tiorfan, Tiorfix. Marketed products are available in capsule form, tablet form and sachet form (used for children) present in the market comprises 100mg, 175mg and 10mg or 30m g Racecadotril respectively.

There are many prior arts disclosing different formulation of Racecadotril as described below: EP1294372 discloses the dry powder formulation of racecadotril which is preferred for pediatric usages. The characteristic of the formulation is that, the Racecadotril granulate prepared with a suitable carrier is coated and mixed with a sweetener. Acrylate and methacrylate polymers especially Eudragit NE 30D are stated as coating agents. According to the procedure, first, racecadotril granulate is prepared with a little sugar, it is coated with a coating agent; the coated granule is mixed with the remaining sugar, aerosil and sweetener and then filled into sachet.

EP2018158 new formulation for Racecadotril in the form of tablets, including the preparation process and their use for treating diarrhea.

W02001097803 describes granulate formulation comprising the anti-diarrhoeal agent racecadotril comprising at least one diluent, at least one lubricant, and an intragranular disintegrant haying defined characteristics.

EP 2462922 discloses formulation of an enkephalinase inhibitor, such as Racecadotril or dexecadotril, the process for the preparation thereof, and the use thereof in the treatment of diarrhoea W02016069871A1 discloses Racecadotril particles. The invention also relates to methods of manufacturing the Racecadotril particles; dosage forms containing the Racecadotril particles; methods of manufacturing the dosage forms, and methods of treatment using the dosage forms.

US9636300B2 describes to lipi d/mi croemulsi on compositions of Racecadotril. More particularly, the present invention relates to lipid/microemulsion compositions containing a pharmaceutical active ingredient and the method of making said compositions US20190021992A1 describes a semi-solid composition comprising at least one Racecadotril and at least one liquid-lipid and/or polyol and/or glycerol and/or propylene glycol excipient, a dose unit comprising the semi-solid composition as well as use and a method of treating a subject suffering from a disease or disorder in the gastro intestinal tract 1N20060165213 discloses a taste -masked composition that comprises particles comprising racecadotril and a low melting excipieni. The composition is prepared by dispersing racecadotril in a melt; cooling the dispersion at room temperature to form a solidified mass, and milling the solidified mass to obtain racecadotril particles.

US20140005262 discloses a composition that comprises racecadotril, at least one surfactant and a lipid.

US20140005261 discloses a liquid composition that comprises Racecadotril and cyclodextrin. 10034] EP2.749270 discloses a dispersible tablet comprising Racecadotril coated with an acrylic acid polymer or a cellulose polymer by a wet granulation method.

However, there are some draw backs with the existing formulations and there is a need for new 30 improved ones.

In seeking to provide suitable formulations for administration to patients it is important to ensure that the formulations are in the most acceptable form to the patient, for example in terms of the nature and appearance of the dosage form, and the ease of ingestion as well as in term of formulation stability.

Inventors of present invention have surprisingly found that stable powder formulation of Racecadotril as described herein

Summary of the Invention

The present invention relates to a stable powder formulation of Racecadotril The main aspect of the present invention is to provide a stable powder formulation of 10 Racecadotril comprising 0.1 to 2% w/w of Racecadotril, 15 to 35% w/w of intra granular sweetener, binder dispersion comprising 1 to 5% w/w of polymer and an auxiliary agent, 60 to 80% w/w of extra granular sweetener, a flavouring agent and a glidant.

Another aspect of the present invention is to provide a process for preparing stable powder formulation of Racecadotril comprising the steps of a. Mixing Racecadotril with intra granular sweetener, one part of glidant and one part of flavouring agent, b. Preparing binder dispersion by adding auxiliary agent in to polymer dispersion, c. Granulating mixture of step a) with step b), d. Drying of mixture of step c), e. Shift the dried granules with 30# sieve, f Mixing sieved powder of step e) with extra granular sweetener and remining flavouring agent, g. Mixing blend of step 0 with remaining glidant.

Detailed description of the Invention

Stable powder formulation of Racecadotril is the invention as further described herein The invention provides a stable powder formulation of Racecadotril comprising of Racecadotril, intra granular sweetener, binder dispersion comprising polymer and an auxiliary agent, extra granular sweetener, a flavouring agent and a glidant The term "pharmaceutically-acceptable salts" as used herein includes salts commonly used to form alkali metal salts and to form addition salts of free acids or free bases. Suitable pharmaceutically-acceptable acid addition salts of Racecadotril may be prepared from an inorganic acid or from an organic acid. Examples of such inorganic acids are hydrochloric, hydrobromic, hydroiodic, nitric, carbonic, sulfuric and phosphoric acid. Appropriate organic acids may be selected from formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucuronic, maleic, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, p-hydroxybenzoic, salicyclic, phenylacetic, mandelic, embonic (pamoic), methanesulfoni c, ethanesulfoni c, 2-hydroxyethanesulfoni c, pantotheni c, benzenesulfoni c, toluenesulfonic, sulfanilic, mesylic, cyclohexylaminosulfonic, stearic, alginic, 13-hydroxybutyric, malonic, galactaric and galacturonic acid. Racecadotril is present in the from of free base.

The term "about" as and where used in this specification means +10% of the mentioned value. However when the term "about" is used in connection with pH, it should be considered as +2 unit of the pH value The terms "formulation" and "composition are intended to have the same meaning and are used interchangeably throughout this specification. The term "suspension" as used herein refers to a system in which small solid particles are essentially uniformly dispersed in a liquid medium.

As used herein, "stable" refers to a composition that is clear to the naked eye and substantially free of chemical degradation of Racecadotril, substantial color change or decrease in dissolution or assay of Racecadotril.

The term "% w/w ' is intended to mean the percentage of an ingredient(s)/the total percentage by weight of the composition (100%) Here the % w/w to be calculated against total weight of composition.

The term Infra granular" means the stage before preparation of granules. The mixture which is to be granulated with binder dispersion. Here in this case, a sweetener is added intra granular means a sweetener is to be added before granulating with binder dispersion.

The term -extra granular" means the stage after preparation of granules. The dried granules prepared after granulation, drying and optionally shifting. Here in this case, a sweetener is added extra granular means a sweetener is to be added to be dried and shifted granules.

The term auxiliary agent" as used herein means an ingredient which work in association with another ingredient to achieve the desired result. It is used in collaboration with another ingredient.

The stable powder formulation of the present invention is chemically and physically stable without any degradation or reduction in dissolution or assay on storage. This was demonstrated in a stability study. Another benefit is that the composition overcame the problem of unpleasant taste.

Racecadotril is a bitter in nature and its difficult to mask the taste for such drug. Further when the drug is presented in powder form, masking of taste is utmost critical parameter.

A stable powder formulation according to the present invention shows good stability and reproducibility even after long-term storage. This means that a stable powder formulation can be stored for a few days or a week or longer without significant degradation.

The stable powder formulation of present invention, even though being in the form of a powder form also offers an advantage of uniform dosing, physical stability. The stable powder form Racecadotril of the present invention, as described herein remains stable for longer period during stability studies performed at different temperature and humidity condition.

As per one embodiment, Racecadotril to be used in the form of Racecadotril free base. The Racecadotril to be used in the range from 0.01 to 10 % w/w, preferably in the range from 0.05 to 5 % w/w, more preferably from 0.07 to 3 % w/w. In a most preferred embodiment, the Racecadotril is present in the range from 0.1 to 2 (l'O w/w.

The stable powder formulation of Racecadotril of the invention remain stable and uniform when appropriate excipients are selected and specific sequence of processing step is followed. Process of preparing the stable powder formulation of Racecadotril also a critical and which result in effective taste masked and stable formulation.

As per one embodiment the stable powder formulation of present invention to effectively mask the taste of Racecadotril, sweetener in proper concentration and proper way to be added.

As per one embodiment, one or more sweetener is to be used.

As per one preferred embodiment, one sweetener is to be added intra granularly and one sweetener is to be added extra granularly. Inventors have tried the different combination of sweetener and sequence of addition of sweetener but only succeeded in few combination and in a specific sequence of adding sweetener.

As per one embodiment intra granular sweetener is selected from sucrose, acesulfame potassium, sucra1ose, cyclamate, saccharin, saccharin sodium and aspartame.

As per one embodiment, intra granular sweetener is present in the range from 10 to 50% w/w, preferably in the range from 15 to 45 % w/w, preferably in the range from 15 to 40% w/w, more preferably in the range from 20 to 35% w/w, more preferably in the range from 15 to 35 % w/w, more preferably in the range from 20 to 30 % w/w.

In a particular embodiment, intra granular sweetener is sucrose and to be present in the range 10 from 20 to 30% w/w.

As per one preferred embodiment, one sweetener is to be added extra granularly and one sweetener is to be added extra granularly.

As per one embodiment, intra granular sweetener is selected from sucrose, acesulfame potassium, sucralose, cyclamate, saccharin, saccharin sodium and aspartame As per one embodiment, intra granular sweetener is present in the range 40 to 85 % -/ preferably in the range from 45 to 85% w/w, more preferably in the range from 50 to 85% w/w, more preferably in the range from 55 to 80 % w/w, more preferably in the range from 60 to 80 In a particular embodiment, extra granular sweetener is sucrose and to be present in the range 20 from 60 to 80% w/w.

If the % w/w of intra granular and extra granular sweetener is exchanged with each other, the final product is not getting the outcome as desired like addition of all sweetener in only intra granular, it is difficult to granulate and if all sweetener is added extra granular, proper flow and uniformity is not observed.

As per one embodiment the binder dispersion is prepared by combination of polymer and an auxiliary agent.

As per one embodiment, polymer is selected from methyl cellulose, hydroxy propyl cellulose, hydroxy propyl methyl cellulose, polyethylene oxide, acrylic and methaciylic acid, copolymers of methyl methacrylate, Poly(ethyl acrylate-co-methyl methacrylate), ethyl acrylate and ethyl 30 cellulose.

As per one embodiment, the polymer is present in the range form 0.1 to 20% w/w, preferably in the range from 0.5 to 15% w/w, preferably in the range from 0.75 to 10 % w/w, more preferably in the range from 1 to 8% w/w, more preferably in the range from 1 to 5% w/w.

As per a particular embodiment, the polymer is Poly(ethyl acrylate-co-methyl methacrylate) and is present in the range from 1 to 5% w/w.

As per one embodiment, an auxiliary agent is selected from sorbitol, mannitol, sucralose, trehalose and lactose. Auxiliary agent is added in binder dispersion and which enhance the binding efficiency and taste masking efficiency.

As per one embodiment, the auxiliary agent is present in the range from 0.1 to 0.3 °,4) w/w.

As per a preferred embodiment, the auxiliary agent is sucralose and is present in the range from 0.1 to 0.3% w/w.

As per one embodiment polymer is Poly(ethyl acrylate-co-methyl methacrylate) which can be used in the powder form and to be dispersed in purified water to prepare dispersion or available ready mix dispersion to be used i.e ACRYCAOTTm E 30 D or EUDRAGITTm NE 30 D. Auxiliary agent is to be added in such dispersion with stirring to prepare homogenous binder dispersion As per one embodiment, flavouring agent is selected from natural or artificial fruit flavour selected from mint (such as peppermint or spearmint), menthol, cinnamon, vanilla, chocolate, bubblegum, cherry, grape, orange, strawberry or lemon.

As per one embodiment, glidant is selected from colloidal silicon dioxide, talc, sodium aluminosilicate, calcium silicate, powdered cellulose, micromystalline cellulose, corn starch, sodium benzoate, calcium carbonate, magnesium carbonate, calcium stearate, magnesium stearate and zinc stearate.

The powder formulation of Racecadotril of present invention is to be added to food, dispersed in a glass of water or in the feeding-bottle, mixing well and followed by immediate administration.

As per one embodiment, the powder formulation of present invention is prepared by method selected from direct compression, dry granulation or wet granulation.

In a preferred embodiment, the powder formulation of present invention is prepared by wet 30 granulation.

As per one embodiment, the stable powder formulation of Racecadotril is prepared by the process comprising the steps of; a. Mixing Racecadotril with intra granular sweetener, b. Preparing binder dispersion by adding auxiliary agent in to polymer dispersion, c. Granulating mixture of step a) with step b), d. Drying of mixture of step c), e. Shift the dried granules with 40# sieve, Mixing sieved powder of step e) with extra granular sweetener and flavouring agent, g. Mixing blend of step 0 with glidant.

As per one preferred embodiment, the stable powder formulation of Racecadotril is prepared by the process comprising the steps of; a. Shifting Racecadotril through 40# and all other ingredients through 604, b. Mixing Racecadotril with intra granular sweetener, c. Preparing binder dispersion by adding auxiliary agent in to polymer dispersion, d. Granulating mixture of step a) with step b), e. Drying of mixture of step c), Shift the dried granules with 40# sieve, g. Mixing sieved powder of step e) with extra granular sweetener and flavouring agent, h. Mixing blend of step 0 with glidant.

As per main embodiment the Racecadotril and flavouring agent along with intra granular sweetener is to be mixed in first step followed by granulating the said mixture with binder dispersion prepared from dispersion of polymer and auxiliary agent. Granules prepared after granulation is to be dried followed by shifting through appropriate # sieve. Dried and shifted granules were then mixed with extra granular sweetener and flavouring agent followed by mixing with glidant.

As per one embodiment, the present invention provide a stable powder formulation of 30 Racecadotril comprising 0.1 to 2% w/w of Racecadotril, 15 to 35% w/w of intra granular sucrose, binder dispersion comprising 1 to 5% w/w of Poly(ethyl acrylate-co-methyl methacrylate)and sucralose, 60 to 80% w/w of extra granular sucrose, a flavouring agent and a gli dant.

As per one embodiment, the present invention provide a stable powder formulation of Racecadotril comprising 0.1 to 2% w/w of Racecadotril, 15 to 35% w/w of intra granular sucrose, binder dispersion comprising 1 to 5% w/w of Poly(ethyl acrylate-co-methyl methaciylate) and sucralose, 60 to 80% w/w of extra granular sucrose, 0.1 to 0.5 ?/1) w/w of flavouring agent and 0.1 to 0.5 % w/w of colloidal silicon dioxide As per one embodiment, the present invention provide a stable powder formulation of Racecadotril comprising 0.5 to 1.5% w/w of Racecadotril, 20 to 30% w/w of intra granular sucrose, binder dispersion comprising 2 to 3% w/w of Poly(ethyl acrylate-co-methyl methaciylate) and sucralose, 65 to 75% w/w of extra granular sucrose, 0.1 to 0.5 % w/w of flavouring agent and 0.1 to 0.5 % w/w of colloidal silicon dioxide.

The invention is further illustrated by the following examples, which are by no means intended to limit the scope of the invention but are given by way of illustration.

Examples

Example 1: Racecadotril Powder (Dry mixing) Ingredients mg/sachet Racecadotril 30.0 Sucrose 294.9 Sucrose 2663.1 Dry lemon flavour 6.0 Anhydrous colloidal silica 6.0 Total 3000.0 Procedure: 1) Racecadotril was mixed with 294.0 mg of sucrose, 2) Blend of step 1) is mixed with 2663.1 mg of sucrose, 3) Blend of step 1) is mixed with dry lemon flavour, 4) Blend of step 1) is mixed with anhydrous colloidal silica.

Observation: The resultant powder showed satisfactory flow property but the taste masking was not achieved.

Example 2: Racecadotril Powder (Dry mixing) with Sucralose Ingredients mg/sachet Racecadotril 30.0 Sucrose 294.9 Sucralose 9.0 Sucrose 2654.1 Dry lemon flavour 6.0 Anhydrous colloidal silica 6.0 Total 3000.0 Procedure: As per Example 1 Observation: The resultant powder showed satisfactory flow property but the taste masking was not achieved.

Example 3: Racecadotril Powder (Wet granulation) Ingredients mg/sachet Infra granular Racecadotril 30.0 Sucrose 287.7 ACRYCOAT E 30 D 30.0 Sucralose 4.2 Extra granular Sucrose 2636.1 Dry lemon flavour 6.0 Anhydrous colloidal silica 6.0 Total 3000.0 Procedure: Racecadotril were shifted through 40 ft and rest all ingredients are shifted through 60ft.

2. Racecadotril mixed with intra granular sucrose, 3. Binder dispersion were prepared by adding ACRYCOAT E 30 D in purified water followed by sucralose in to polymer dispersion, 4. Mixture of step I) was granulated with dispersion of step 2), 5. Mixture of step 3) were dried, 6. Dried granules were shifted through 30# sieve, 7. Sieved powder of step 5) were mixed with extra granular sucrose and Dry lemon flavour, 8. Mixing blend of step 6) with Anhydrous colloidal silica.

Observation: The resultant powder showed satisfactory flow property and taste masking was also achieved but little bitter after taste was observed.

Example 4: Racecadotril Powder (Wet granulation) Ingredients mg/sachet Intra granular Racecadotril 30.0 Sucrose 750.0 ACRYCOAT E 30 D 75.0 Sucralose 4.2 Extra granular Sucrose 2128.8 Dry lemon fl avour 6.0 Anhydrous colloidal silica 6.0 Total 3000.0 Procedure: As per Example 3 Observation: The resultant powder showed satisfactory flow property and desired taste masking was also achieved with palatable taste. Composition of Example 4 was charged for stability Initial result of Example 4 composition.

Result Blend Uniformity 100.2% Assay 100.4% Dissolution 84.0% Example 5: Analysis of Marketed formulation Hidrasec 10mg Hidrasec 30mg (Racecadotril) (Racecadotril) Batch No.: SXN582 SXE2114 Assay Analysis -1 Analysis -2 Analysis -1 Analysis 2 87.3% 93.0% 92.1% 89.3% Dissolution 88.1% 86.6%

Claims

Claims 1. A stable powder formulation of Racecadotril comprising 0.1 to 2% w/w of Racecadotril, 15 to 35% w/w of intra granular sweetener, binder dispersion comprising 1 to 5% w/w of polymer and an auxiliary agent, 60 to 80% w/w of extra granular sweetener, a flavouring agent and a gli dant.
2. The stable powder formulation of Racecadotril according to claim 1, wherein Racecadotril is present in free base form.
3. The stable powder formulation of Racecadotril according to claim 1, wherein intra granular sweetener is selected from sucrose, acesulfame potassium, sucralose, cyclamate, saccharin, saccharin sodium and aspartame.
4. The stable powder formulation of Racecadotril according to claim 1, wherein intragranular sweetener is sucrose and present in the range from 20 to 30% w/w.
5. The stable powder formulation of Racecadotril according to claim 1, wherein polymer is selected from methyl cellulose, hydroxy propyl cellulose, hydroxy propyl methyl cellulose, polyethylene oxide, acrylic and methacrylic acid, copolymers of methyl methacrylate, Poly(ethyl acrylate-co-methyl methacrylate), ethyl acrylate and ethyl cellulose.
6. The stable powder formulation of Racecadotril according to claim 1, wherein auxiliary agent is selected from sorbitol, mannitol, sucralose, trehalose and lactose.
7. The stable powder formulation of Racecadotril according to claim 1, wherein extra granular sweetener is selected from sucrose, acesulfame potassium, sucralose, cyclamate, saccharin, saccharin sodium and aspartame.
8. The stable powder formulation of Racecadotril according to claim 1, wherein extra granular sweetener is sucrose and present in the range from 60 to 80% w/w.
9. The stable powder formulation of Racecadotril according to claim 1, wherein flavouring agent is selected from natural or artificial fruit flavour selected from mint (such as peppermint or spearmint), menthol, cinnamon, vanilla, chocolate, bubblegum, cherry, grape, orange, strawberry or lemon.
The stable powder formulation of Racecadotril according to claim 1, wherein glidant is selected from colloidal silicon dioxide, talc, sodium aluminosilicate, calcium silicate, powdered cellulose, microcrystalline cellulose, corn starch, sodium benzoate, calcium carbonate, magnesium carbonate, calcium stearate, magnesium stearate and zinc stearate.
11 The stable powder formulation of Racecadotril according to claim 1, wherein powder is prepared by wet granulation.
12 A stable powder formulation of Racecadotril comprising 0.1 to 2% w/w of Racecadotril, 15 to 35% w/w of intra granular sucrose, binder dispersion comprising 1 to 5% w/w of Poly(ethyl acrylate-co-methyl methacrylate)and sucralose, 60 to 80% w/w of extra granular sucrose, a flavouring agent and a glidant.
13 A stable powder formulation of Racecadotril comprising 0.1 to 2% w/w of Racecadotril, 15 to 35% w/w of intra granular sucrose, binder dispersion comprising 1 to 5% w/w of Poly(ethyl acrylate-co-methyl methacrylate) and sucralose, 60 to 80% w/w of extra granular sucrose, 0.1 to 0.5 % w/w of flavouring agent and 0.1 to 0.5 % w/w of colloidal silicon dioxide.
14 A process for preparing stable powder formulation of Racecadotril comprising the steps of a. Mixing Racecadotril with intra granular sweetener, b. Preparing binder dispersion by adding auxiliary agent in to polymer dispersion, c. Granulating mixture of step a) with step b), d. Drying of mixture of step c), e. Shift the dried granules with 30 sieve, f Mixing sieved powder of step e) with extra granular sweetener and flavouring agent, g. Mixing blend of step with glidant.